The authors cloned and generated the sequence of the lin-14 gene. They discovered that a
segment in lin-14 mRNA (messenger RNA), was necessary for its inhibition by lin-4.

Ruvkun and Ambros (No. 14010) then compared results and shared the sequences of lin-4 and lin-14 genes and noticed that the short lin-4 mRNA matched complementarity sequences in the critical segment of the lin-14 mRNA. Both performed further experiments showing that the lin-4 microRNA turns off the lin-14 by binding to the complementary sequences of its mRNA thus blocking the production of lin-14 protein.

Ambros and Ruvkun concurrently discovered a novel principle of gene regulation,
mediated by a previously unknown type of RNA that they named "microRNA."
Initially the scientific community considered their data a peculiarity of the C.
elegans worm and likely irrelevant to humans and other more complex animals. 

In 2024 Ruvkun and Ambros shared the Nobel Prize in Physiology or Medicine for "the discovery of microRNA and its role in post-transcriptional gene regulation."

Order authorship in the original publication: Wightman, Ha, Ruvkun.

(Thanks to Juan Weiss for this reference and its interpretation.)

Working with the let-7 gene, the authors led by Ruvkun showed that microRNA encoded by the let-7 gene was highly conserved, and present throughout the animal kingdom, proving that gene regulation by microRNA is universal among unicellular organisms on Earth. This paper, published seven years after the initial discovery (No. 14301) provided the evidence to convince skeptics of the existence of microRNA.

Order of authorship in the original publication: Pasquinelli, Reinhart, Slack, Ruvkun.

(Thanks to Juan Weiss for this reference and its interpretation.)